Bispecific antibodies have been used to redirect the antigen specificity of PBL from normal human donors, so that they become cytotoxic for an allogeneic ovarian carcinoma cell line. The altered lymphocytes can kill the tumor cells in vitro and block intraperitoneal growth of an established tumor in immunodeficient mice. The degree of antitumor activity depends on the types of lymphocytes in the donor sample, the procedure used to make the bispecific antibodies, and the techniques used to activate the lymphocytes in vitro prior to use in the experiments. A natural mechanism for nonspecifically activating MHC-independent cytotoxic cells and CTL is indicated by results of in vitro studies carried out with mouse cells. The mechanism is initiated by polyanions and low levels of lipopolysaccharides, such as may occur from naturally resident bacterial flora. The response to these activating factors utilizes ancillary cells, primarily B lymphocytes and T-helper cells, in addition to the precursors to the activated cytotoxic cells.